Proteomic Tools for the Quantitative Analysis of Artificial Peptide Libraries: Detection and Characterization of Target-Amplified PD-1 Inhibitors.
dynamic combinatorial chemistry
molecular recognition
peptides
protein-protein interactions
proteomics
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
20 06 2022
20 06 2022
Historique:
revised:
31
03
2022
received:
16
03
2022
pubmed:
2
4
2022
medline:
23
6
2022
entrez:
1
4
2022
Statut:
ppublish
Résumé
We report a quantitative proteomics data analysis pipeline, which coupled to protein-directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein-protein interaction (PPI) modulators. A low-affinity PD-1 binder was incubated with a library of >100 D-peptides under thiol-exchange favoring conditions, in the presence of the target protein PD-1, and we determined the S-linked dimeric species that resulted, amplified in the protein samples versus the controls. We chemically synthesized the target dimer candidates and validated them by thermophoresis binding and protein-protein interaction assays. The results provide a proof-of-concept for using this strategy in the high-throughput search of improved drug-like peptide binders that block therapeutically relevant protein-protein interactions.
Identifiants
pubmed: 35362647
doi: 10.1002/cbic.202200152
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Peptide Library
0
Peptides
0
Programmed Cell Death 1 Receptor
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200152Informations de copyright
© 2022 Wiley-VCH GmbH.
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